The excretion of ammonium by the mammalian kidney constitutes a major defense against systemic acidosis and involves the synthesis of ammonia by renal tubular cells with its subsequent transfer into tubular fluid. Ammonia is synthesized by the kidney from glutamine and its product glutamate. In metabolic acidosis, ammonia production by the kidney is increased and contributes significantly to the maintenance of acid-base homeostasis. In chronic renal disease, a diminished ammonia production underlies the development of metabolic acidosis. Although several factors have been shown to play a role in the control of renal ammoniagenesis no single factor can explain the observed metabolic events. In recent years, extensive investigation has accumulated defining mechanisms of anion transport across mitochondrial membranes. The role of these processes in the control of renal ammoniagenesis has not been extensively explored. We propose to identify the mechanisms of glutamine and glutamate transport across the mitochondrial membrane of rat kidneys. Glutamate and aspartate flux will be measured to identify a postulated glutamate-hydroxyl and glutamate-aspartate transport carrier. The influence of these carriers on glutamate uptake and oxidation by mitochondria will be tested at different H ion concentrations. Glutamine transport and the glutamine-glutamate antiporter will be characterized. The changes in and control of the mitochondrial redox state in acidosis will be explored. These studies will be extended to kidney mitochondria from rats with acute and chronic acidosis in vivo and with uremia. These studies will provide insight into the biochemical mechanisms underlying the control of renal ammoniagenesis.